Method for the production of 2-isopropyl-4-methyl-6-hydroxypyrimidine

Abstract

A process is described for the production of 2-isopropyl-4-methyl-6-hydroxypyrimidine (oxypyrimidine) by reacting isopropylamidine in an alkaline lower alkanol solvent system with an alkyl acetoacetate to close the ring and form the oxypyrimidine in a continuous flow multi-stage reactor (MSR) under controlled multi-stage conditions whereby the reactants contact each other in each of said stages under conditions which reduce the possibility of the formation of unwanted reaction products from said reactants in said solvent system.

What is claimed is: 
     
       1. A process for preparing an oxypyrimidine-type compound of the formula: ##STR5## where P is selected from the group consisting of isopropyl, cyclopropyl and n-propyl-, which comprises the steps of reacting an amidine hydrochloride of the formula: ##STR6## with an acetoacetic ester of the formula: ##STR7## where Alk is methyl or ethyl, to effect ring closure by introducing an alkali-neutralized methanolic solution of said amidine hydrochloride to a temperature range of -5° C. to 15° C. together with said acetoacetic ester into the first stage of a multi-stage reactor, this multi-stage reactor comprising a series of chambers (stages) connected by restricted flow orifices to ensure limited dwell time for the reactants at each stage but preventing back mixing of the incoming raw materials, flowing said mixture of reactants into the second stage of said multi-stage reactor away from the zone of reactant introduction; adjusting the pH in said second stage to 12.0±1 with caustic solution to initiate said ring closure reaction while maintaining a temperature in said second stage at 40°±5° C.; flowing said reaction mixture maintained at said temperature and pH to at least one successive stage; holding said reaction mixture of each of said successive stages for at least 2-8 minutes until the ring closure reaction at the last stage is complete. 
     
     
       2. The process according to claim 1 where the oxypyrimidine-type compound is 2-isopropyl-4-methyl-6-hydroxypyrimidine. 
     
     
       3. The process according to claim 2 wherein said neutralized methanolic amidine solution is introduced into the first stage of said multi-stage reactor at a temperature of about 0°-5° C. 
     
     
       4. The process according to claim 2 wherein said multi-stage reactor contains ten stages. 
     
     
       5. The process according to claim 4 wherein the holding time at each of the stages of said multi-stage reactor  is 5 minutes to a total reaction time in said multi-stage reactor of about 50 minutes. 
     
     
       6. The process according to claim 2 wherein said last stage is carried out in a polishing holding tank at pH 12.0±1.0 and 40°-45° C. until said reaction is completed. 
     
     
       7. The process according to claim 6 wherein the holding time in said polishing tank is at least one hour. 
     
     
       8. The process according to claim 2 wherein the temperature in said second stage is maintained at 40°±2° C.